17-丙烯胺基-17-去甲氧基格尔德霉素对原发性肝癌细胞增殖侵袭的抑制作用

目的 观察17-丙烯胺基-17-去甲氧基格尔德霉素(17AAG)对肝癌细胞的增殖、侵袭和转移能力的抑制作用.方法 检测1μmol/L 17AAG对细胞增殖、侵袭能力和凋亡的影响,观察0.1 μmol/L和1.0μmol/L 17AAG对其靶点热休克蛋白(HSP) 90表达的影响.结果 17AAG对HL7702肝脏细胞无生长抑制作用,对肝母细胞瘤细胞HepG2 24、48和72 h IC50值分别为( 14182.94 ±6369.90)、(1.56±0.19)和(0.02±0.00) μmol/L]和肝癌细胞MHCC-97H 24、48和72 h IC50值分别为(5660.49±3029.33)、(3.30±0.31)和(1.55±0.12) μmol/L]均有生长抑制作用,影响细胞周期,降低其离散和侵袭的能力,并诱导凋亡,对裸鼠皮下移植瘤生长具有抑制作用,降低肿瘤的肺、肝转移.17AAG上调HSP90的表达.结论 17AAG对HepG2细胞和MHCC-97H细胞具有增殖抑制、诱导凋亡和降低转移能力的作用,而对HL-7702肝脏细胞则无生长抑制及诱导凋亡的作用.

Inhibitory effect of 17AAG on proliferation and invasion of hepatocellular carcinoma cells

Objective To observe whether 17AAG can inhibit the proliferation,invasion and metastatic ability of hepatocellular carcinoma (HCC) cells.Methods The changes of proliferative and invasive abilities and apoptosis of HCC cells treated with 1 μmol/L 17AAG were tested.The change of HSP90 expression in HCC cells treated with 0.1 and 1.0 μmol/L 17AAG was detected by using Western blotting.Results There was no growth inhibition in HL7702 hepatocytes.17AAG could inhibit the growth of HepG2 cells IC50 of 24,48 and72 h:(14182.94 ±6369.90),(1.56±0.19) and (0.02±0.00)μmol/L] and MHCC-97H cells IC50 of 24,48 and 72 h:(5660.49 ± 3029.33 ),(3.30 ± 0.31 ) and ( 1.55 ±0.12) μmol/L],and decrease the ability of scattering and invasion.17AAG also affected the cell cycle and induced apoptosis of HepG2 and MHCC-97H cells.17AAG inhibited the growth of transplanted tumors in nude mice and the metastasis of the lung and liver.The expression of HSP90 was elevated by 17AAG.Conclusion 17AAG inhibited the proliferation and metastatic ability of HepG2 and MHCC-97H cells,and induced apoptosis.However,there were no growth inhibition and apoptosis induction in HL7702 hepatocytes.